Inverse changes in fetal insulin-like growth factor (IGF)-1 and IGF binding protein-1 in association with higher birth weight in maternal diabetes

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Abstract

Objective

The insulin like growth factor (IGF) system plays a key role in regulating fetal growth, is metabolically regulated, and may influence development of increased birth weight in offspring of mothers with diabetes. We examined IGF-1 and IGF binding protein-1 (IGFBP-1) concentrations in cord blood samples from offspring of mothers with gestational and type 2 diabetes.

Design and patients

Case-control study of Maori and Pacific Island mothers recruited prospectively at Middlemore Hospital, South Auckland, New Zealand.

Measurements

Cord blood (for insulin, IGF-1 and IGFBP-1) was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation from138 mothers with gestational diabetes (GDM), 39 mothers with type 2 diabetes (T2DM) and 95 control mothers.

Results

Babies born to mothers with both GDM and T2DM had significantly increased birth weight (Z-score birth weight mean ± SD: GDM 0·94 ± 1·31, T2DM 0·53 ± 1·1) compared to controls (Z-score birth weight −0·08 ± 1·10). IGFBP-1 was significantly reduced in both diabetic groups (median interquartile range: GDM 67(31–137) ng/ml, T2DM 59(29–105) ng/ml, control 114(56–249) ng/ml). Cord IGF-1 was significantly increased in cord blood of infants of mothers with GDM (42·2 ± 16·3 ng/ml vs. control 34·7 ± 18·5 ng/ml) but not T2DM (38·7 ± 17·4 ng/ml). In all offspring, IGF-1 and IGFBP-1 were positively and negatively correlated with birth weight, respectively.

Conclusions

Maternal diabetes results in inverse changes of circulating fetal IGF-1 and IGFBP-1 at birth. A decrease in circulating IGFBP-1 and to a lesser extent an increase in circulating IGF-1 may present an important mechanism that contributes to increased birth weight in diabetic pregnancies.

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